Delayed neurological deterioration in the absence of direct spinal cord insult following surgical decompression is a severe postoperative complication in patients with chronic severe spinal cord compression (SCC). The spinal cord ischemia-reperfusion injury (IRI) has been verified as a potential etiology of the complication. However, the exact pathophysiologic mechanisms of the decompression-related IRI remain to be defined. In this study, we developed a practical rat model of chronic severe SCC. To explore the underlying role of inflammation in decompression-related IRI, immunoreactivity of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) before and after decompression were measured. In addition, expression level of TNF-a, and IL-1 beta was examined with Western blot. Immunohistochemical staining showed negative result in gray matters in the sham group and sham-decompression group. In the severe compression group, strong positive staining of TNF-a and IL-1 beta were found, suggesting a dramatic infiltration of inflammatory cells in gray matters. Furthermore, the severe compression group showed a significant increase in expression level of TNF-alpha and IL-1 beta as compared with the sham group (p < 0.05). In the severe compression-decompression group, both immunostaining and Western blot showed significant increase of TNF-a and IL-1 beta levels in the spinal cord compared with the severe compression group (p < 0.05). The results demonstrated that surgical decompression plays a stimulative role in inflammation through increasing the expression of inflammatory cytokines in the rat model of chronic severe SCC injury. Inflammation may be one of the important pathological mechanisms of decompression-related IRI of chronic ischemia.